1. Field of the Invention
The field of this invention relates to testing equipment and more particularly to an apparatus which is useable to determine the transfer of a substance through a membrane into a liquid placed in contact with the opposite side of the membrane.
2. Description of Prior Art
Percutaneous absorption test cells are used in the study of kinetics of the partition coefficients defining the passage and equilibrium of components from one side to the other side of a barrier separatinq two dissimilar substances. A typical test cell is known as the "Franz" cell. The Franz cell is in the form of a container with an upper half separated from a lower half by a porous membrane comprising a barrier. A clamping arrangement is located between the upper half and the lower half with the barrier in the form of a thin sheet material film to be placed and clamped tightly in a stretched configuration by a clamping means located between the upper half and lower half of the Franz cell.
The lower half of the Franz cell container is completely filled with a receptor liquid with this liquid to be in contact with the barrier. Within the upper half is to be placed a donor substance which may comprise a solid, semi-solid, gas or liquid. The receptor normally comprises water, a buffered solution or a saline solution. Connecting with the lower half is a sample port and it is through this sample port that aliquots are to be removed. An aliquot is defined as an exact sub-volume of the overall volume of the receptor liquid. This sample port, in the Franz cell, may also be used to add additional receptor liquid.
While generally useful in the whole field of physical chemistry, Franz cells have become particularly useful in the healthcare field. Transfer kinetics of active substances through the human skin must be determined. Levels of epidermal exposure to pesticides, chemicals, ointments and cosmetics are important in the field of environmental science.
Also, the usage by human beings of prolonged release medications depends on the specific knowledge of a secure prediction of the transfer kinetics a active ingredients penetrate through the skin. Medicinal skin patches have been used for some time by human beings and every year a greater number of such patches are being used. It is necessary to know exactly the amount of active ingredients that will penetrate the user skin within a given amount of time. This information is essential to determine the size of the skin patch and the amount of dosage.
Within a Franz cell, typically the test is conducted by placing the donor material against the total area of the barrier. A typical donor material would be a medicated ointment. A receptor fluid, such as a saline solution, is placed within the receptor chamber in contact with the barrier. All air bubbles are to be removed from the receptor liquid so there is not any air bubble in contact with the barrier as such air bubbles will affect inaccurately the transfer characteristics. There is a stirring device utilized within the receptor chamber which is operated to homogeneously intermix the donor substance as it permeates the membrane into the receptor chamber. At predetermined intervals, aliquots are withdrawn through the sample port for analysis. After an aliquot is withdrawn, such is replaced by an equivalent amount of fresh receptor fluid.
In removing of the aliquot, it is important that the volume removed is not so great as to decrease the overall volume of the receptor fluid to the point to where air would be permitted to enter the receptor chamber. If the desired sample volume is large enough to lower receptor volume to allow bubbles to enter the cell, it is necessary to add replacement fluid between withdrawals. If there is only a single Franz cell utilized and the removal of the aliquot is accomplished manually, generally it would be easy for the user to ensure that the volume would be not so great as to permit air to enter the receptor chamber. However, in common practice, the withdrawal of the aliquots is accomplished from an array of Franz cells with an aliquot being removed from each Franz cell. Therefore the causing of air to enter the receptor chamber can occur rather easily. The reason that a plurality of Franz cells are utilized is to provide a plurality of readings of a quantity of donor substance that penetrates the barrier within a given period of time and then to take an overall average so as to arrive at accurately as possible the transfer characteristics of the active ingredients of the donor substance into the receptor fluid.
After the aliquot is withdrawn, as previously mentioned, an equal quantity of fresh receptor fluid is to be then supplied to each Franz cell. When the fresh receptor fluid is to be supplied, a given period of time must occur so that the stirring device will evenly mix the new receptor fluid with the receptor liquid that is contained within the receptor chamber. In order to provide adequate time to evenly mix the fresh receptor fluid with the older receptor fluid, it is common to permit as much as thirty minutes for homogeneous intermixing to occur. It is frequently desirable to remove aliquots spaced only a few minutes from each other. Therefore, the time of achieving homogeneous intermixture of thirty minutes is just not acceptable.